While histamine has satisfied many of the basic requirements of a neurotransmitter in the brain, very little is known regarding the participation of histaminergic neurons in the function of discrete neuronal circuits. The proposed studies will address biochemical and morphological aspects of histaminergic neurons with respect of vasopressin- oxytocin- and corticotropin releasing factor (CRF)-producing neurons in the hypothalamus. A monoclonal antibody to histidine decarboxylast (HDC, the enzyme that synthesized histamine from histidine) will be used in immunohistochemical studies of histaminergic neurons. Immunohistochemical studies at the level of the light microscope will address the distribution of histaminergic neurons and the relative frequency of HDC-containing varicosities in apposition to vasopressin-, oxytocin- and CRF- producing neurons. Ultrastructural analysis of HDC-immunoreactive varicosities will determine the synaptic relationships of HDC-containing terminals to neurons and glia within a nucleus which contains vasopressin and oxytocin neurons. Receptor autoradiography of H1 histamine binding sites will address the relative distribution of H1 receptors among neurons and glia within the hypothalamus, and the proportion of these receptors that may occur on catecholaminergic terminals within the paraventricular nucleus. Dynamic aspects of histaminergic neurons in the hypothalamus will be addressed by determining the effect of stimuli which alter the release of vasopressin, oxytocin and CRF on HDC activity and numbers of H1 binding sites. A microassay for HDC will be used to determine changes in enzyme activity in microdissected supraoptic and paraventricular nuclei in response to experimental stimuli. Receptor autoradiography will be used to determine correlations in changes in numbers of H1 binding sites associated with vasopressin-, oxytocin- and CRF-producing neurons, specifically, in response to the same stimuli. Therefore, these studies will provide important information regarding the participation of histaminergic neurons in the regulation of discrete neuroendocrine systems.